A. Field of the Invention
The invention generally relates to therapeutic compositions of matter, methods for producing said compositions, and methods for administering said composition to living organisms, including human beings. Particularly, the several embodiments of the invention allow protection of an organism against viral attack by stimulation of the cells of the organism to cause said cells to product an antiviral protein known as interferon.
B. Description of the Prior Art
Interferon is an antiviral protein released by animal cells in response to viral infection. It has long been known that RNA is a specific virion component which triggers the release of interferon in animal cells, both natural and synthetic double-stranded RNA's being known to stimulate interferon production. These double-stranded RNA molecules have not found utility as chemotherapeutic agents due to the toxicities thereof, such toxicity being related primarily to the presence of the double-helical RNA structure. It has been recently shown that the first step in interferon induction in the cells of a living organism, i.e., the absorption of the nucleic acid complex of polyinosinic acid annealed to polycytidylic acid (rI.sub.n.rC.sub.n), is a rapid event, thereby suggesting that an intact primary structure of the inducer complex be present only for a brief period in the cell. The present invention now concludes that, once interferon induction is triggered, the continued presence of double-helical RNA is unnecessary and leads to secondary effects on the cell without increasing the magnitude of antiviral resistance. The invention thus involves provision of double-stranded nucleic acid complexes which, while retaining the capability of inducing interferon production in cells, are capable of being readily hydrolyzed by nucleases in the cells. Such nucleic acid complexes are duplications of the double-stranded virus genes which promote interferon production during viral attack, but which are modified to thereby be rendered less toxic to the cells due to the ability of said modified complexes to be more readily destroyed within the cells. The compounds of this invention have been disclosed previously from the laboratories (J. Molecular Biology 70:568[1972]), published Oct. 31, 1973.
In addition, now a new type of hypoxanthihepolynucleotides has been synthesized from a mixture of inosine 5'-diphosphates and 2'-O-methylinosine 5'-diphosphates with M. Luteus polynucleotide phosphorylase. The procedure is similar to that previously disclosed from the laboratories (Biochemistry 11, 4931 [1972]). This type of hypoxanthine-polynucleotides contain 5-16% 2'O-methylinosine residues together with 95-84% inosine residues correspondingly, designated as (rI.sub.5.sub.-20, 2'-MeI).sub.n. These complexes, (rI.sub.5.sub.-20, 2'-MeI).sub.n.rC.sub.n, are 100-fold more active than the rI.sub.n.rC.sub.n as interferon induces to human cells. Apparently this modification of the backbone of polyinosinate strand has a pronounced enhancement effect; therefore a less amount of (rI.sub.5.sub.-20,2'MeI).sub.n.rC.sub.n is needed then r I.sub.n.rC.sub.n in protecting the human cells against viral diseases.